Steroid hormone compositions in medium chain oils

• US 10,286,077 B2
• Filed: 03/30/2017
• Issued: 05/14/2019
• Est. Priority Date: 04/01/2016
• Status: Expired due to Fees

• Current Assignee: TherapeuticsMD Inc.
• Original Assignee: TherapeuticsMD Inc.
• Inventors: Shadiack, Annette, Persicaner, Peter H. R., Inskeep, Philip B., Thorsteinsson, Thorsteinn, Sancilio, Frederick D., Legassie, Jason D.
• Primary Examiner(s): Chu, Yong L
• Application Number:
  US15/473,742
• Publication Number:
  US 20170281776A1
• Time in Patent Office: 775 Days
• Field of Search: 514177
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

This disclosure provides a novel pharmaceutical composition capable of forming micelles upon exposure to the gastric environment. The pharmaceutical composition is suitable for delivering steroid hormones, and progesterone in particular, to a subject in need thereof.

Claims

1. A method of treating a disease or condition associated with reduced progesterone levels, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising:

about 6 weight percent progesterone,

from about 1 weight percent to about 15 weight percent of a polysorbate, and

from about 70 weight percent to about 90 weight percent of a medium chain oil,

wherein

the medium chain oil comprises at least about 50 weight percent of a predominantly medium chain monoglyceride and up to about 10 weight percent of a complex medium chain diglyceride; and

the progesterone is fully solubilized.

3. The method of claim 1, wherein the disease or condition associated with reduced progesterone levels is selected from the group consisting of menopause, endometrial hyperplasia;

secondary amenorrhea;

prevention of preterm birth; and

osteoporosis.

5. The method of claim 1 wherein the predominantly medium chain monoglyceride and the progesterone are present at a weight ratio of about 10:

1 to about 15;

1.

6. The method of claim 1, wherein the medium chain oil comprises at least about 70 weight percent of a predominantly medium chain monoglyceride.

7. The pharmaceutical composition of claim 6, wherein the polysorbate is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80.

8. The method of claim 1, wherein the pharmaceutical composition provides an oral bioavailability of at least about 150 percent as measured by an increase in AUC when compared to a reference product.

9. The method of claim 1, wherein the pharmaceutical composition further comprises at least one of a polyoxyethylene hydrogenated castor oil, a D-α

-Tocopherol polyethylene glycol succinate derivative, or a terpene.

10. The method of claim 9, wherein the predominantly medium chain monoglyceride comprises at least about 90 weight percent of the medium chain oil.

11. The method of claim 10, wherein the polysorbate is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80.

12. The method of claim 9, wherein the pharmaceutical composition provides an oral bioavailability of at least about 150 percent as measured by an increase in AUC when compared to a reference product.

2. A method of treating a disease or condition associated with reduced progesterone levels, the method comprising administering to a subject in need thereof an oral, fully-solubilized progesterone pharmaceutical composition comprising:

a polysorbate and about 6 weight percent progesterone, wherein the progesterone and the polysorbate are present in a weight ratio of from about 1;

2 to about 2;

1; and

a medium chain oil comprising at least about 50 weight percent of a predominantly medium chain monoglyceride and up to about 10 weight percent of a complex medium chain diglyceride, the medium chain oil not containing more than about 10 weight percent triglycerides.

4. The method of claim 2, wherein the disease or condition associated with reduced progesterone levels is selected from the group consisting of menopause, endometrial hyperplasia;

secondary amenorrhea;

prevention of preterm birth; and

osteoporosis.

13. The method of claim 2, wherein the polysorbate is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80.

14. The method of claim 2, wherein the pharmaceutical composition provides an oral bioavailability of at least about 150 percent as measured by an increase in AUC when compared to a reference product.

15. The method of claim 2, further comprising at least one of a polyoxyethylene hydrogenated castor oil, a d-α

-tocopherol polyethylene glycol succinate derivative, or a terpene.